1. Field of the Invention
The present invention relates generally to medical methods and kits. More particularly, the present invention relates to methods and kits for flushing an interior lumen of an implanted catheter prior to closing the catheter between successive uses.
Implanted catheters enjoy widespread use in a number of medical procedures. For example, intravenous (IV) therapy relies on long-term implantation of a venous catheter to deliver fluids, medications, and other substances to a patient. Hemodialysis and hemofiltration both rely on separate draw and return catheters implanted in a vein to allow extra corporeal treatment of the blood. Peritoneal dialysis, in contrast, relies on a single catheter implanted in the peritoneum to permit introduction and withdrawal of dialysate to permit in situ dialysis.
The need to leave catheters implanted over long periods of time raises a number of concerns. For example, the catheters can become infected requiring treatment of the patient and often times removal of the catheter. This is a particular problem with transcutaneous catheters where the skin penetration is a common route of infection. Secondly, implanted catheters can often become plugged or fouled over time. This is a particular problem with intravascular catheters where clotting and thrombus formation within the catheter lumen can be problematic.
To reduce problems associated with thrombus formation, it is now common to xe2x80x9clockxe2x80x9d intravascular access catheters between successive uses. Locking typically involves first flushing the catheter with saline to remove blood and other substances from the catheter lumen. After the catheter has been flushed, an anti-coagulant solution, typically heparin, is then injected to displace the saline and fill the lumen. The heparin-locking solution both excludes blood from the lumen and actively inhibits clotting and thrombus formation within the lumen. While some thrombus may still form at the distal tip of the catheter, the formation is usually minimal and presents few problems. It has further been proposed to combine various anti-microbial substances with the locking solution in order to inhibit infection at the same time that thrombus is being inhibited.
While generally effective, the use of heparin locks suffers from a number of disadvantages. The need to prepare a heparin solution at the end of every catheter treatment session is time-consuming and presents an opportunity for error by a caregiver. Hemodialysis and hemofiltration patients will have to undergo such heparin locks at least several times a week, while patients on IV may have to undergo such heparin locks several times a day. Over time, the inconvenience and expense of performing heparin locks can build up. Moreover, the need to combine a separate anti-microbial agent in the heparin lock solution further complicates the procedure and adds expense, and the addition of an anti-microbial agent to the heparin lock will generally be effective only within the lumen and at the openings from the lumen. There will be little reduction in the risk of infection in the regions surrounding the implanted catheter, including at the point of penetration through the skin where the risk of infection is the greatest.
For all these reasons, it would be desirable to provide improved methods, compositions, and kits for locking implanted catheters between successive uses. Such locking methods should inhibit fouling of the catheter lumens and eradicate existing infections and/or reduce the chance of potential infections. In particular, such methods, compositions, and kits should be easy to implement, require minimum or no preparation, be of low cost, and be useful with most or all types of implanted catheters, including hemodialysis and hemofiltration catheters, IV catheters, peritoneal dialysis catheters, and the like. At least some of these objectives will met by the inventions described hereinafter.
2. Description of the Background Art
U.S. Pat. No. 4,929,242 describes a solution containing glycerol and having a density similar to that of blood for providing a heparin lock on an intravenous catheter. U.S. Pat. No. 5,077,281 describes an anti-microbial solution containing a taurolin compound for inhibiting coagulation in dialysis catheters and other vascular prostheses. PCT WO 00/01391 describes an anti-microbial lock comprising a taurinamide derivative. Commonly assigned U.S. Pat. Nos. 5,807,356; 5,931,829; 5,989,239; 5,997,524; 6,007,5165; 6,120,492; 6,132,415; and 6,193,684; and co-pending patent application Ser. Nos. 09/003,772; and 09/161,044, are relevant to the present application. All of the above patents and pending applications are incorporated herein by reference.
The present invention provides methods and kits for the improved locking and/or disinfection of subcutaneously and transcutaneously implanted catheters. The catheters typically will have a distal end which is open to a body lumen. Most commonly, the catheters will be intravascular catheters where the distal end is implanted in or attached to a blood vessel, usually a vein, but in some cases an artery. Exemplary intravascular catheters include hemodialysis and hemofiltration catheters, intravenous catheters, and the like. Intravenous catheters can be used for a wide variety of purposes, including fluid infusion, drug delivery, and the like. Catheters attached other than to the vasculature include peritoneal dialysis catheters which are open to the peritoneal cavity, and the like.
The catheters which are treated by the methods of the present invention may be transcutaneously implanted or subcutaneously implanted. By xe2x80x9ctranscutaneously implanted,xe2x80x9d it is meant that the distal end of the catheter is attached to or implanted within a target body lumen and a proximal end of the catheter is located externally to the patient. An intermediate portion of the catheter will thus pass through or penetrate the patient""s skin, and the proximal end of the catheter will usually have a hub to permit selective attachment of infusion tubes, syringes, solution bags, and the like. Most commonly, the proximal attachment hub will have a luer fitting. By xe2x80x9csubcutaneously implanted,xe2x80x9d it is meant that the entire catheter is implanted beneath the skin and no portion of the catheter extends through the skin. Such subcutaneously implanted catheters are typically attached to a fully implanted hub at their proximal ends. The hub permits percutaneous access via a needle or other penetrating element. After a treatment session is finished, the needle or other penetrating element is removed and all portions of the catheter and proximal hub are then located beneath the skin. Examples of such subcutaneously implanted catheters and proximal access hubs are described in the commonly assigned, copending applications described above, as well as U.S. Pat. No. 5,807,356, the full disclosures of which have previously been incorporated herein by reference.
As described in the Background section above, both transcutaneously and subcutaneously implanted catheters are subject to fouling and plugging, particularly in and about their distal ends which are implanted in or attached to a blood vessel or other body lumen. To reduce the risk of such fouling, the present invention provides methods, compostions, and kits for filling a lumen of the implanted catheter with a solution of a lower alcohol and an additive. The lower alcohol is typically ethanol, propanol, or butanol, with isopropanol being the preferred alcohol. Surprisingly, it has been found that these lower alcohols are effective in inhibiting fouling and plugging of the lumen, particularly in inhibiting clot formation within the lumens of intravascular catheters. The ability to inhibit clot formation without the need to prepare and use heparin solutions is a significant advantage. Moreover, the lower alcohols have the additional ability to eradicate existing infections and/or inhibit potential infections. The additive may comprise either an anti-microbial substance, typically taurolidine or triclosan, or an anti-coagulant substance, typically riboflavin, sodium citrate, ethylene diamine tetraacetic acid, or citric acid. This solution combination of a lower alcohol and an additive is particularly effective since alcohol increases the effectiveness of the anti-microbial or anti-coagulant additives, while the additives in return reduce the possible toxic effects of the alcohol. Thus, both the reduction of catheter fouling and the eradication and/or inhibition of infection can be achieved with the use of commonly available, widely accepted materials which are introduced to the catheter lumen in a convenient fashion, as described in more detail below.
The ability to eradicate existing infections and/or inhibit potential infections of the implanted catheter can be improved by utilizing catheters where at least a portion of the catheter body permits the lower alcohol to permeate the catheter body and, preferably, pass outwardly into the tissue region surrounding the catheter. The catheter body may be porous or substantially non-porous (i.e. still permits sufficient diffusion of the lower alcohol, typically from a distal tip of the catheter into the tissue region surrounding the tip). While the use of such catheter bodies can be beneficial with many anti-microbial locking solutions, such as that taught in U.S. Pat. No. 5,077,281, the full disclosure of which has been incorporated herein by reference, it is particularly useful with the lower alcohols of the present invention. It will be appreciated that the lower alcohols have relatively low molecular weights and polar structures which will enable them to readily penetrate into and optionally through many porous or partially porous materials. Exemplary porous materials for construction of the catheter body include silicone rubber, expanded PTFE (e.g., GORE-TEX(copyright), medical membranes) and the like. Such materials may be formed into the tubular catheter bodies or may be incorporated as separate component(s) into the catheter bodies.
In a first aspect, a locking composition for filling an implantable catheter comprises at least one lower alcohol in a range from 1% to 99% by volume and at least one other anti-microbial or anti-coagulant compound in a range from 1% to 99% by volume. The lower alcohol is selected from the group consisting of ethanol, propanol, and butanol, with the presently preferred alcohol being isopropanol. The lower alcohol will usually be in aqueous solution, typically at 1% to 99% by volume, usually from 5% to 95% by volume. The at least one other anti-microbial is selected from the group consisting of taurolidine and triclosan, and the at least one anti-coagulant is selected from the group consisting of riboflavin, sodium citrate, ethylene diamine tetraacetic acid, and citric acid. The implantable catheter may be a transcutaneous catheter attached at its distal end to a body lumen, typically a blood vessel, the peritoneal cavity, or the like. Alternatively, the implantable catheter may be a subcutaneously implantable catheter which is attached at its distal end to a blood vessel, the peritoneal cavity, or the like. The locking composition may be used with porous or substantially non-porous catheter bodies, as described above.
In a second aspect, a locking composition comprises one lower alcohol in a range from 1% to 99% by volume and at least one other anti-microbial or anti-coagulant compound in a range from 1% to 99% by volume. The lower alcohol is selected from the group consisting of ethanol, propanol, and butanol, with isopropanol being the preferred alcohol. The at least one other anti-microbial is selected from the group consisting of taurolidine and triclosan, and the at least one anti-coagulant is selected from the group consisting of riboflavin, sodium citrate, ethylene diamine tetraacetic acid, and citric acid. A preferred concentration of the anticoagulant is about 4% by volume. Most preferably, the concentration of the locking composition comprises isopropanol by about 17.5% volume and sodium citrate by about 4% weight to volume.
In a third aspect, a method according to the present invention for disinfecting an implanted catheter comprises introducing an anti-microbial solution into a lumen of the catheter, wherein at least a portion of the catheter permits sufficient diffusion of the anti-microbial solution outwardly from the lumen into the catheter body, and preferably into tissue surrounding the catheter to eradicate an existing infection. Exemplary and preferred anti-microbial solutions include at least one lower alcohol, preferably ethanol, propanol, or butanol, and most preferably isopropanol. The solution may further comprise at least one other anti-microbial, preferably taurolidine or triclosan, or anti-coagulant compound, preferably riboflavin, sodium citrate, ethylene diamine tetraacetic acid, or citric acid, as described above. The implanted catheters may be subcutaneously or transcutaneously implanted.
In a forth aspect of the present invention, a kit for disinfecting an implantable catheter comprises a container (optionally a syringe) holding a volume of a solution of a lower alcohol and instructions for use. The instructions set forth a method comprising introducing the solution into a lumen of the catheter, wherein at least a portion of the catheter permits sufficient diffusion of the solution outwardly from the lumen into the catheter body, and preferably into tissue surrounding the catheter to eradicate an existing infection. The kit may further comprise a package for holding both the container and the instructions for use, such as a box, tray, tube, pouch, or the like. The lower alcohol is typically selected from the group consisting of ethanol, propanol, and butanol, with isopropanol being the preferred alcohol. The volume of the solution in the container is typically in the range from 1 ml to 20 ml, preferably from 2 ml to 10 ml, usually being about 2 ml to 4 ml. Additionally, the container will usually comprise a syringe to permit direct introduction of the solution into the implantable catheter.